PubMed Health⌕ Search

Biomedical subjects

J F Brien

Publications and source records attributed to J F Brien.

72 records · Page 4Linked to original sources
PubMed1985

Gas-liquid chromatographic analysis of ethanol and acetaldehyde in blood with minimal artifactual acetaldehyde formation.

A gas-liquid chromatographic procedure utilizing headspace gas analysis is described for the determination of ethanol and its metabolite, acetaldehyde, in a 100-microliters sample of blood from the rat, guinea pig, sheep, or human. Artifactual formation of ethanol-derived acetaldehyde is minimized during sample preparation by using a chemical solution containing perchloric acid and sodium azide in saline, and thiourea. Aqueous standards of ethanol and acetaldehyde are used to calibrate the procedure, and 1-propanol is used as the internal standard of the method. The recovery of ethanol and acetaldehyde from spiked blood samples is quantitative and reproducible, with a within-day coefficient of variation of less than 7% for ethanol and less than 9% for acetaldehyde. The lower limit of quantitative sensitivity is 0.006 mg/ml ethanol and 0.10 microgram/ml acetaldehyde. The instrumental analysis time is less than 3 min, which enables high sample throughput.

Acetaldehyde↗
PubMed1985

Differential pharmacokinetics for oral and intraperitoneal administration of ethanol to the pregnant guinea pig.

The disposition of ethanol was studied in third-trimester pregnant guinea pigs (56-59 days gestational age) following maternal administration of ethanol, 0.5 g/kg total body weight, by oral intubation and by intraperitoneal injection. For oral administration, exposure of the fetus to ethanol involved bidirectional placental transfer of ethanol between the maternal and fetal compartments. For ip administration, there was distribution of ethanol from the peritoneal space across the uterus and chorioamniotic membranes into the amniotic fluid in addition to absorption into the maternal blood circulation and subsequent placental transfer into the fetus. This resulted in exposure of the fetus to very high ethanol concentration in the amniotic fluid immediately following ethanol administration. The data indicate that the ip route of ethanol administration does not mimic ingestion of ethanol and should be avoided in future studies of the fetal alcohol syndrome in rodent animal models.

Administration, Oral↗
PubMed1985

A comparative study of the inhibition of hepatic aldehyde dehydrogenases in the rat by methyltetrazolethiol, calcium carbimide, and disulfiram.

Methyltetrazolethiol (1-methyl-5-mercapto-1,2,3,4-tetrazole, MTT) is a heterocyclic substituent of the cephalosporin antibiotics, cefamandole, cefoperazone, and moxalactam. Pretreatment of rats with MTT has been reported to increase blood acetaldehyde concentration after ethanol administration. The time course of MTT-induced inhibition of hepatic aldehyde dehydrogenases (ALDH) was determined in adult, male Sprague-Dawley rats in comparison with the hepatic ALDH inhibition induced by calcium carbimide (calcium cyanamide, CC) and disulfiram (D). The apparent onset of maximal inhibition of hepatic low Km ALDH occurred at 2 h for 50 mg/kg MTT (subcutaneous, s.c.) and 7 mg/kg CC (oral) and at 24 h for 300 mg/kg D (oral). The relative magnitude of maximal inhibition of low Km ALDH was CC greater than D greater than MTT. The relative duration of enzyme inhibition was D greater than MTT greater than CC. High Km ALDH was only inhibited by CC. Hepatic low Km ALDH was selectively inhibited by s.c. and oral administration of 125 mg/kg MTT. For s.c. administration of 125 mg/kg MTT, the magnitude of maximal enzyme inhibition and the duration of inhibition were greater than for the 50 mg/kg dose. Oral administration of 125 mg/kg MTT produced similar inhibition of hepatic low Km ALDH compared with s.c. administration of the same dose. The time course of blood ethanol and acetaldehyde concentrations was determined for the intravenous infusion of two 0.3-g/kg doses of ethanol to rats that were pretreated orally with saline (1 h), MTT (125 mg/kg, 2 h), or CC (7 mg/kg, 1 h). The relative increase in blood acetaldehyde concentration compared with saline pretreatment was CC greater than MTT. The elimination of ethanol from blood was slower in the MTT- and CC-pretreated animals, and this effect was more pronounced for CC pretreatment. Overall, the data demonstrate that the characteristics of hepatic ALDH inhibition for MTT are different from those of the known ALDH inhibitors, CC and D.

Acetaldehyde↗
PubMed1985

Cerebral metabolism in fetal lamb after maternal infusion of ethanol.

Cerebral uptake of glucose and O2 (VCO2) was measured in 10 chronically catheterized fetal lambs during a control period, after a 1-h maternal infusion of ethanol (1.0 g X kg-1 X h-1) and 1-h postethanol infusion, to determine if alterations in cerebral metabolism might occur. Brachiocephalic artery and sagittal vein blood samples were analyzed for glucose, O2 content, blood gases, pH, and ethanol. Cerebral blood flow (Qc) was measured with a radioactive microsphere technique. VCO2 decreased significantly, from 140 +/- 13 mumol X 100 g-1 X min-1 during the control period to 91 +/- 8 (P less than 0.05) with the ethanol infusion, with a related fall in Qc, 177 +/- 12 to 104 +/- 9 ml X 100 g-1 X min-1 (P less than 0.001), the cerebral arteriovenous O2 difference being little changed. Cerebral glucose uptake, although decreased, was not significantly changed with the ethanol infusion, because the cerebral arteriovenous difference for glucose increased with the related fall in Qc. We conclude that maternal infusion of ethanol results in a decreased fetal VCO2 with a related fall in Qc. If prolonged, this decrease in cerebral oxidative metabolism might well affect cerebral development and provide a mechanism whereby chronic alcohol intake contributes to central nervous system growth anomalies and dysfunction of infants exposed to alcohol in utero.

Animals↗
PubMed1985

Role of hemoglobin in the differential biotransformation of glyceryl trinitrate and isosorbide dinitrate by human erythrocytes.

Incubation of 2 X 10(-7) M glyceryl trinitrate (GTN) at 37 degrees C with human red blood cells resuspended in saline resulted in a 73.4 +/- 3.5% (S.D.) elimination of GTN after 10 min. The elimination of GTN was accompanied by the appearance of an equimolar amount of the GTN metabolites. The biotransformation of GTN and another organic nitrate, isosorbide dinitrate (ISDN), was examined in more detail using the 25,000 X g supernatant fraction of human red blood cells (RBC-SF). Incubation of 2 X 10(-7) M GTN or ISDN at 37 degrees C with RBC-SF resulted in a 46.3 +/- 7.3% (S.D.) elimination of GTN after 40 min and a 51.8 +/- 5.9% (S.D.) elimination of ISDN after 240 min. The elimination of the parent organic nitrate was accompanied by the appearance of an equimolar amount of metabolites. The biotransformation of ISDN was inhibited completely by pretreatment of the RBC-SF with trypsin, N-ethylmaleimide or heating at 65 degrees C, whereas GTN biotransformation was only inhibited partially by these treatments. Biotransformation of GTN was inhibited partially by pretreatment of the RBC-SF with CO or potassium ferricyanide; these treatments had no effect on ISDN biotransformation. Treatment of the RBC-SF with the combination of N-ethylmaleimide plus CO or trypsin plus CO resulted in complete inhibition of GTN biotransformation. We conclude that ISDN biotransformation by erythrocytes is a sulfhydryl-dependent enzymatic process, whereas the biotransformation of GTN is due to a combination of a sulfhydryl-dependent enzymatic process and an interaction with reduced hemoglobin.

Adult↗
PubMed1979

The calcium carbimide-ethanol interaction: effects of ethanol dose.

In a double-blind, placebo-controlled study involving five male alcoholic volunteers, oral administration of 0.7 mg/kg of calcium carbimide (CC) 12 hr before ingestion of ethanol (0.125, 0.25, and 0.5 gm/kg) produced an interaction consisting of increased blood acetaldehyde level, tachycardia, and decreased diastolic blood pressure. The order of intensity of the interaction with regard to ethanol dose was 0.5 greater than 0.25 greater than 0.125 k gm/kg. The subjects were aware of a CC-ethanol interaction only for 0.25 and 0.5 gm/kg of ethanol, for which heart rate was elevated above 100 bpm. With the criterion of heart rate above 100 as indicative of the CC-ethanol interaction, the onset was 0.25 and 0.38 hr for the 0.5 and 0.25 gm/kg ethanol doses and the duration of the interaction was 1.0 and 0.38 hr, respectively. There were positive linear correlations between blood acetaldehyde level and both heart rate and pulse pressure. There was appreciable individual variability in the intensity and duration of the interaction. Pretreatment with CC reduced the rate of ethanol metabolism at the 0.5 gm/kg ethanol dose.

Acetaldehyde↗
PubMed1978

A study of the calcium carbimide-ethanol interaction in man.

In six male alcoholic volunteers, oral administration of calcium carbimide (0.7 mg/kg) before ingestion of ethanol (0.5 g/kg) produced an interaction consisting of increased blood acetaldehyde level, tachycardia and increased pulse pressure, which was due mainly to decreased diastolic blood pressure. For these experimental conditions, calcium carbimide had a duration of action of at least 24 h to produce an interaction with ethanol. The order of intensity of the interaction with regard to the calcium carbimide pretreatment time interval was 4 greater than 8 approximately 12 greater than 24 h. Using the criterion of heart rate above 100 as indicative of the calcium carbimide-ethanol interaction, the onset was 0.13, 0.25, 0.25 and 0.38 h for the 4-, 8-, 12- and 24-h pretreatment experiments and the duration of the interaction was 1.6, 1.0, 1.0 and 0.12 h, respectively. There were positive linear correlations between acetaldehyde level and heart rate and between acetaldehyde level and pulse pressure. There was appreciable interindividual variability in the heart rate and blood pressure responses. Increased blood acetaldehyde level seemed to be required for the physiological changes to occur. Calcium carbimide pretreatment at the 4-h interval produced increased blood ethanol level for the last hour of the interaction and reduced the rate of ethanol metabolism.

Acetaldehyde↗
PubMed1978

Methamphetamine-induced behavioural effects and brain concentrations of methamphetamine and its metabolite amphetamine in mice.

(+)-Methamphetamine (MA) produced dose-related behavioural changes in mice. There was a correlation between the type of behavioural response and the peak brain MA concentration after the i.p. administration of each of the following doses of (+)-MA: 0.64 mg/kg (decreased quiescence--0.738 microgram/g MA), 2.5 mg/kg (increased locomotor activity--3.148 microgram/g MA) and 10.0 mg/kg (stereotyped behaviour--12.608 microgram/g MA). During the 90-min experimental period, there was no positive correlation between the magnitude of each type of drug-induced behaviour and the brain MA concentration. For 10.0 mg/kg (+)-MA, there was a negative correlation between the drug-induced stereotyped behaviour and the brain MA concentration. The apparent disappearance half-life of MA from brain was dependent on the dose of (+)-MA: 0.64 mg/kg (t1/2 56.6 min), 2.5 mg/kg (t1/2 66.6 min), 10.0 mg/kg (42.2 min). For the three (+)-MA doses, the metabolite amphetamine (A) also was present in the brain and the A/MA + A brain concentration ratio was 0.11--0.14. This metabolite appeared to have only a small involvement in the MA-induced behavioural effects.

Amphetamine↗
PubMed1977

A comparative study of the behavioural responses induced by chronic administration of methamphetamine and amphetamine in mice.

The behavioural effects induced in mice by the chronic administration of (+)-methamphetamine (MA) and (+)-amphetamine (A) at three dosages were studied under identical research conditions. The results indicated that MA exerted greater central excitation than A. At the dosage 0.64 mg/kg quiescence was decreased and activity increased more by MA than A. Hyperactivity induced at the 2.5 mg/kg dosage was sustained over a longer time period with MA. Frenzied self-tearing emerged with repeated drug administration at the 10 mg/kg dose in more MA-treated than A-treated animals.

Animals↗
PubMed1976

Measurement of acute and chronic behavioural effects of methamphetamine in the mouse.

A simple and reliable method was developed for rating the dose-related behavioural effects of methamphetamine in male Swiss Albino mice for acute or chronic drug treatment. This procedure was based on a frequency count of certain behaviours made at 15-min intervals over a 90-min period following drug administration. The Fisher Randomization procedure was adapted to analyze behavioural data for the chronic studies. Clear-cut, dose-related behavioural responses occurred following acute (+)-methamphetamine administration and ranged from decreased quiescence (0.64 mg/kg) through increased locomotor activity (2.5 mg/kg), a mixture of stereotyped behaviour and increased locomotor activity (5.0 and 7.5 mg/kg), to primarily stereotyped gnawing, licking or sniffing (10 mg/kg). In studies involving chronic administration of (+)-methamphetamine at 0.64, 2.5 and 10 mg/kg conducted over six and seven weeks, behavioural responses were more exaggerated than in acute studies. All behaviours returned to normal levels in the recovery week except for locomotor activity at the 10 mg/kg dosage. In some animals, chronic treatment with 10 mg/kg (+)-methamphetamine led to protracted self-tearing that replaced the gnawing, licking, sniffing stereotype.

Animals↗
PubMed1975

Comparative drug elimination in man-diphenylhydantoin and amobarbital.

The concentration of 5,5-diphenylhydantoin (DPH) in serum was determined at selected time intervals in seven healthy male volunteers starting 10 h after an oral dose of 400 mg sodium DPH was given. The data were analyzed according to a one-compartment model assuming first-order kinetics. The mean serum half-life was 19.28 h +/- 5.87 (SD). A positive correlation coefficient (r=0.84, p less than 0.05) was found between the serum DPH half-life and the serum amobarbital half-life in the seven subjects. The urinary levels of free plus conjugated 5-(p-hydroxyphenyl)-5-phenyl-hydantoin were determined for 12 h periods over a minimum of two days following the 400 mg oral dose of sodium DPH. Subjects with a short DPH half-life tended to excrete in urine a greater amount of p-HPPH as compared to subjects with a long DPH half-life. In the case of one subject, the urinary excretion of p-HPPH plateaued five days after DPH administration and the apparent elimination half-life determined from the p-HPPH urinary excretion data was 19.16 h as compared to the value of 19.53 h calculated from the DPH serum levels.

Adult↗
PubMedDate not supplied

Determination of isosorbide dinitrate biotransformation in various tissues of the rabbit by capillary column gas-liquid chromatography.

A selective and sensitive capillary column gas-liquid chromatographic procedure has been developed for the simultaneous determination of isosorbide dinitrate (ISDN) and its mononitrate metabolites in rabbit blood and tissue homogenates. The method has a limit of detection of 0.1 ng ml-1 for ISDN, 1 ng ml-1 for isosorbide 5-mononitrate (5-ISMN), and 2 ng ml-1 for isosorbide 2-mononitrate (2-ISMN). The day-to-day coefficients of variation were 2.5, 6.8, and 11.3 per cent for ISDN, 5-ISMN, and 2-ISMN, respectively. The within-day coefficients of variation were 2.7, 4.9 and 6.5 per cent for ISDN, 5-ISMN, and 2-ISMN, respectively. The procedure was used to determine the biotransformation of ISDN (2 X 10(-7) M) to 5-ISMN and 2-ISMN by various rabbit tissue homogenates. The relative rate of biotransformation of ISDN was liver greater than lung approximately equal to intestine greater than kidney greater than blood approximately equal to skeletal muscle, with the lung and intestine homogenates being about two-thirds as active as liver homogenates. These results indicate that extrahepatic biotransformation of ISDN, especially by lung and intestine, may contribute to the systemic clearance of ISDN in the rabbit.

Animals↗
PubMedDate not supplied

Fetal guinea pig brain 15-hydroxyprostaglandin dehydrogenase: ontogeny and effect of ethanol.

The objectives of this study were to determine the ontogeny of 15-hydroxyprostaglandin dehydrogenase (15-OH-PGDH) activity in the brain of the fetal guinea pig and to test the hypothesis that acute in vitro ethanol exposure produces concentration-dependent inhibition of fetal brain 15-OH-PGDH activity. Enzyme activity was determined in vitro by measuring the rate of oxidation of PGE2 to 15-keto-PGE2 using an optimized radiometric procedure. The study was conducted utilizing the whole brain of the fetal guinea pig at mean gestational ages of 34, 43 and 62 days (term, about 66 days) and the brain stem (pons and medulla) of the fetal guinea pig at mean gestational ages of 43 and 62 days. The direct effect of acute in vitro exposure to ethanol was assessed by incubating 15-OH-PGDH with ethanol in the concentration range of 10 to 80 mM. 15-OH-PGDH was measurable in the whole brain and brain stem, and the enzyme activity was similar for the gestational ages examined. There was no significant ethanol-induced inhibition of 15-OH-PGDH activity in the whole brain or brain stem. The data demonstrate that the whole brain and brain stem of the fetal guinea pig have the capacity to metabolize PGE2 to 15-keto-PGE2, an inactive metabolite, during the second half of gestation. The data apparently are not consistent with the hypothesis that acute in vitro exposure to ethanol directly inhibits 15-OH-PGDH activity in fetal brain.

Animals↗
PubMedDate not supplied

Disposition of amiodarone and its proximate metabolite, desethylamiodarone, in the dog for oral administration of single-dose and short-term drug regimens.

A comparative study of the plasma disposition and tissue distribution of amiodarone and its proximate metabolite, desethylamiodarone, for a single oral dose and short-term oral dosage regimens was conducted in the dog. Four groups of male mongrel dogs (six per group) received one of the following oral dosage regimens: single dose of 40 mg amiodarone/kg; 40 mg amiodarone/kg/day for 10 days and then 30 mg/kg/day for 4 days; 40 mg amiodarone/kg/day for 10 days, 30 mg/kg/day for 4 days, and then no treatment for 14 days; and 40 mg amiodarone/kg/day for 10 days, 30 mg/kg/day for 4 days, and then 20 mg/kg/day for 5 days/week for 2 weeks. The plasma and tissue amiodarone and desethylamiodarone concentrations were determined by HPLC. The plasma concentration of amiodarone was greater than that of desethylamiodarone for the four dosage regimens. The apparent plasma elimination half-life of amiodarone was prolonged following repeated drug administration (3.2 days) compared with a single drug dose (7.5 hr). There was extensive extravascular distribution of amiodarone and desethylamiodarone resulting in progressive tissue accumulation of drug and metabolite for the short-term regimens. For most of the dosage regimens, the concentration of amiodarone was greater than that of desethylamiodarone in left and right ventricles, thyroid gland, adipose tissue, and kidney, whereas the parent drug and metabolite concentrations were similar in lung, liver, and brain. There was predominant accumulation of amiodarone in adipose tissue and desethylamiodarone in lung. After cessation of amiodarone administration, there was rapid elimination of parent drug and metabolite from all tissues, except for amiodarone from adipose tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMedDate not supplied

Disposition of ethanol and its proximate metabolite, acetaldehyde, in the near-term pregnant ewe for short term maternal administration of moderate-dose ethanol.

The effect of short term maternal ethanol administration on the disposition of ethanol in the ovine maternal-fetal unit was determined. Eleven conscious instrumented near-term pregnant ewes (between 125 and 134 days of gestation; term, 147 days) received 1-hr iv infusion of 1 g of ethanol.kg of maternal body weight-1.day-1 for six days (N = 6 ewes) or an equivalent volume of saline for six days (N = 5 ewes). On the seventh day, the ethanol- and saline-pretreated animals were administered 1 g of ethanol.kg of maternal body weight-1. Ethanol and acetaldehyde concentrations were determined by headspace GLC in maternal blood, fetal blood, and amniotic fluid samples obtained at selected times during the 14-hr study. The data demonstrated that short term maternal administration of once-daily moderate dose ethanol did not produce major changes in the disposition of ethanol and its proximate metabolite, acetaldehyde, in the maternal, fetal, and amniotic fluid compartments during near-term ovine pregnancy.

Acetaldehyde↗